The work proposed in this application deals with three closely related areas. Comprising the great majority of the overall effort are studies that attempt to generate, in vitro, cytotoxic T lymphocytes against autologous or HLA identical leukemic cells. Methods to be used for this purpose include mixed leukocyte culture-cell mediated lympholysis assays, growth of cells in T cell growth factor and cloning of the T lymphocytes at various stages following generation. Protocols are proposed that attempt to optimize the specificity of the cytotoxic T lymphocytes that are generated as well as to obtain an understanding of the target determinants recognized by such effector cells. The balance between help and suppression, as it relates to the generation of the cytotoxic T lymphocytes will be investigated in a series of experiments in mouse. The other two projects deal first with the use of antisera, presumably directed at the HLA-DR antigens, to study both expression of such antigens on T lymphocytes and to manipulate the immune response by removing from precursor populations suppressor T lymphocytes as well as, perhaps, helper T lymphocytes; and second, with induction of xenogeneic tolerance in mice against human cell surface antigens in an attempt to obtain both serological and cellular reagents that are reactive with antigens of interest on both responding cells in the in vitro assays employed as well as on stimulating cells, such as leukemia cells.